Stereoelectronic stabilization

In his analysis of transition states (Z)-ll and ( )-ll, Keck pointed out that in (Z)-ll, the a-carbon of the (Z)-crotyltri-n-butylstannane is farther from the aldehyde oxygen in transition state (Z)-ll than is the a-carbon of the ( )-crotyltri- -butylstannane in transition state ( -11, and thus is less able to participate in secondary orbital overlap interactions. The decrease in stereoelectronic stabilization of transition state (Z)-ll, compared to ( )-ll, allows access to other competing transition states which can lead to the diastereomeric anti homoallylic alcohol 3 (e.g. transition. states 13 or 14, Fig. 11-3, see above) in the reactions of the (Z)-crotylstannane reagent. Also, the (Z)-crotyltri-n-butylstannane in transition state (Z)-ll probably experiences increased steric interactions with the aldehyde R group relative to ( l)-crotyltri-n-buty]stannane in transition state ( )-ll. 

A detailed NMR study of the mechanism of ribozymomimetic phos-phonylation with phosphorus acid and two oxiranes revealed consecutive formation of p-hydroxy-if-phosphonate monoesters (38a,b), di-(P-hydroxyalkyl)-H-phosphonates (39a,b), alkylene-H-phosphonates (40a,b), p-hydroxyalkylalky-lene phosphites (41a,b) and the corresponding stereoelectronically-stabilized H-tetraoxaspirophosphoranes (42a,b). The equilbrium between (41 a,b) and (42a,b) shifts towards (41a,b) at higher temperature. " ... 

In oxazolidines, the extent of ring chain tautomerism is also governed both by the acidity of its a-CH and by stereoelectronic stabilization of acyclic tautomers. Deprotonation at the a-carbon of the C-2 appendage induces ring opening of the oxazolidine to its chain tautomer. In 27a and 27b, steric hindrance to deprotonation and possible nonplanarity of the carbanion system due to the orthogonal disposition... 

Despite the great amount of interest in reductive desulfonylation reactions, very little research has addressed the stereospecific reductive desulfonylation of chiral a-substituted sulfones. Only limited success has been achieved as shown in Eq. 30.50 Lithium naphthalenide is used for the stereoselective SET desulfonylation of anomeric sulfones derived from 2-deoxy-D-glucose derivatives.51-54 The initial homolytic cleavage of the C-SO2 bond generates a cr-radical, which adopts an a-orientation due to stereoelectronic stabilization,55-57 forcing the anomeric substituent to adopt the (3-orientation, an arrangement that is retained through the reduction process (Eq. 31). 

Another illustrative example of the gauche effect is provided by trans-1,2 difluorocyclohexane (Figure 6.24a). In this case, stereoelectronic stabilization for the gauche conformation is smaller than in 1,2-diflnoroethane since it comes from the a. interactions that are less effective than o interactions in 1,2-... 

A more detailed discussion of the scenarios for the evolution of stereoelectronic effects in chemical reactions will be given in Chapter 10. It is important to keep in mind that transition state stabilization is the most direct way to decrease activation barriers. Like catalysts that have to express their love for substrates in the TS, the stereoelectronic effects also have to reach maximum magnitude at the TS in order to have an accelerating effect on the reaction. Like catalyst affinity to the ground state, stereoelectronic stabilization of reactants is not kinetically productive. 

Figure 10.5 The ground state structural distortion and dominant force of TS stereoelectronic stabilization are the same ground state geometry predicts correct reaction product.

State structural distortion and the dominant force of TS stereoelectronic stabilization coincide, trends in the ground state geometry correctly predict the observed reaction product. 

Thermodynamic control of reactivity - control of reactivity by an external switching off a stereoelectronic effect The simple comparison of electronic effects in reactant and product is sufficient for reactions that proceed under thermodynamic control. It is common for chemical reactions to proceed from reactants that have relatively weak stereoelectronic stabilization to products where such stabilization is stronger. In such situations, switching off a stereoelectronic effect can be used to reverse position of equilibrium between two common functional groups. As is well-known, amides are more stable than esters due to the greater magnitude of the n, c=o interaction in amides in comparison to the n, Jt c=o interaction... 

Attenuated stereoelectronic stabilization of intermediate = lower tor 2" step... 

In summary, this mechanistic hypothesis has a number of stereoelectronic features that are tightly coordinated to create an efficient enzymatic process. Formation of H MPT via removal of the axial C-H is favored by the combined stereoelectronic assistance of the lone pairs of the three nitrogen atoms. However, the fnU power of snch assistance in an enzyme would be counterproductive because it would overstabilize the cationic part of the catalytic cycle. Instead, the enzyme imposes a non-planar conformation where excessive stereoelectronic stabilization is avoided. This system illnstrates an interesting connection between geometry, reactivity and enzymatic fnnction. 

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